Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

Abstract

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

Exclusion ofRPGRIP1ins44 from Primary Causal Association with Early-Onset Cone–Rod Dystrophy in Dogs

“…1,2 In terms of CRD, the standard wire-haired dachshund, miniature long-haired dachshund (MLHD), Glen of Imaal terrier, and pit bull terrier are the only dog breeds thus far affected, and the genes involved have been identified in all but pit bull terriers. [3][4][5][6] Of these, a severe early-onset CRD (cord1) was described in MLHDs 5 and the locus mapped to a region of canine chromosome 15 (CFA15) orthologous to human chromosome 14 (HSA14).…”

Identification of Genetic Variants in <I>PDC, RHO, PDE6A</I> and <I>PDE6B</I> in Dogs with Progressive Retinal Atrophy

“…The genetic variation underlying some forms of progressive retinal atrophy can be mapped to the chromosomal location of others using molecular techniques 1 . SNPs are present to a greater extent than microsatellite and are distributed across the genome to aid association studies 7 . A definite advantage of GWAS over Linkage Association (LA) study is that it does not essentially require large and multigenerational pedigrees.…”

“…Over the past two decades, a number of approaches have been used to search for candidate genes and mutations underlying various traits in dogs. Different mutations have been identified underlying retinal diseases in 58 dog breeds using genome-wide association studies (GWAS), linkage study and targeted gene approach 7 . Although several mutations have been identified in PRAs, the genetic cause of PRA in many breeds is unknown 8 .…”

Atrofia progressiva generalizada da retina em cães da raça Cocker Spaniel

“…Atrofi a progressiva generalizada da retina é uma doença genética, de caráter autossômico recessivo, que pode acometer cães da raça Cocker Spaniel (MIYADERA et al, 2012). Resulta em perda progressiva da função retiniana externa e morte dos fotorreceptores bilateralmente, tendendo à simetria e sem predisposição sexual (BEDFORD, 2005;TUNTIVANICH et al, 2009).…”

“…Nos cães da raça Cocker Spaniel Inglês e Americano, a doença ocorre por uma distrofi a dos fotorreceptores (CÔCO et al, 2009). Clinicamente, observa-se midríase bilateral com perda da visão noturna (nictalopia) e posteriormente perda da visão diurna (acromatopsia) (MIYADERA et al, 2012).…”